Amol Akhade: Insights on KEYNOTE-689 immunotherapy breakthrough in non-metastatic HNSCC at AACR 2025
Amol Akhade, Consultant Medical Oncologist and Hemato-oncologist at Suyog Cancer Clinics, shared a post on LinkedIn:
“Immunotherapy (IO) in Non-Metastatic Head and Neck Cancer: A Turning Point?
Until now, IO struggled to find success in non-metastatic HNSCC:
- JAVELIN Head and Neck 100 (avelumab + CRT) – failed to improve PFS
- KEYNOTE-412 (pembrolizumab + CRT) – failed to improve EFS
But at AACR25, we witnessed a probable game-changer:
- KEYNOTE-689 (perioperative pembrolizumab) met its primary endpoint, demonstrating significant improvement in Event-Free Survival (EFS)!
What was different about KEYNOTE-689?
(And why did it succeed while others failed?)
- Neoadjuvant immunotherapy: 2 cycles of pembrolizumab before surgery to prime the immune system.
- Surgical debulking: Major tumor burden removed before adjuvant therapy, creating a more favorable tumor microenvironment.
- Adjuvant pembrolizumab + radiotherapy: IO intelligently combined with postoperative RT, rather than during heavy CRT upfront.
- Perioperative IO strategy: IO before and after surgery – not just during CRT – leading to more sustained immune activation.
- Biomarker guidance: Enrichment based on PD-L1 CPS ≥10 in major pathological response (mPR) analysis.
Key Clinical Lessons:
Timing matters – IO around surgery can be more effective than during concurrent CRT. Biology matters – Tumor microenvironment post-surgery may be more ‘immune hot’. Strategy matters – Smarter trial designs are changing the game.
And the story is just beginning!
At ASCO25, the community awaits results from the Nivolumab post-operative trial – bringing more questions than answers about the best IO timing and combinations in HNSCC!
Incredible times for head and neck oncology research!”
Amol Akhade highlighted the results of the KEYNOTE-689 trial presented at AACR 2025, where perioperative pembrolizumab improved event-free survival in non-metastatic head and neck cancer. The strategy differed from previous trials by integrating neoadjuvant immunotherapy, surgical debulking, and postoperative radiotherapy, emphasizing timing, tumor biology, and smarter trial designs.
More posts featuring Amol Akhade.
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Challenging the Status Quo in Colorectal Cancer 2024
December 6-8, 2024
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ESMO 2024 Congress
September 13-17, 2024
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ASCO Annual Meeting
May 30 - June 4, 2024
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Yvonne Award 2024
May 31, 2024
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OncoThon 2024, Online
Feb. 15, 2024
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Global Summit on War & Cancer 2023, Online
Dec. 14-16, 2023